Abstract Human papilloma virus (HPV) and herpes simplex virus (HSV) infections account for significant morbidity in men who have sex with men (MSM). HPV is associated with oral, oropharyngeal, and anal cancers and a growing body of research suggests racial disparities in HIV burden may be partially attributed to HSV infection. Building on our ongoing cohort study (the P18 cohort study; R01DA025537) of young MSM (YMSM), we will assess anal and oral HPV, HSV-1, and HSV-2 over time. Applying a syndemic theory framework will allow examination of sociodemographic, biological, behavioral, psychosocial and structural determinants of these viral infections. Our work is informed by findings generated from the P18 cohort study including persistence of inadequate sexual health care in YMSM, incident HIV infections (7.2% to date), and a high level of infection with bacterial sexually transmitted infections (STIs) including chlamydia, gonorrhea, and syphilis. Moreover, recent evidence suggests YMSM have a very low likelihood of initiating HPV vaccination. Thus, understanding HPV and HSV infection as well as correlates and predictors will yield a more comprehensive understanding of the multiple health burdens impacting the health of YMSM. Second, understanding HPV and HSV infection in YMSM may shed light on the stark racial/ethnic disparities in HIV in YMSM. The proposed ancillary study is guided by the following aims: (1) To describe the epidemiology of overall, high-risk, low-risk, and vaccine preventable HPV infection as well as HPV vaccination uptake and completion in a racially/ethnically diverse sample of YMSM; specifically, to: (1a) estimate prevalence & incidence of anal, oral and paired co-infection of nonavalent vaccine-type HPV infection as well as correlates and risk factors for prevalent, incident, persistent, and cleared infections; (1b) prospectively estimate HPV infection and persistence as risk factors for HIV; and (1c) determine multi-level facilitators and barriers to HPV vaccination uptake and completion quantitatively and qualitatively via in-depth interviews with a sub-sample of study participants. (2) To describe the epidemiology of HSV-1 and HSV-2 in a racially/ethnically diverse sample of YMSM; specifically, to (2a) estimate prevalence & incidence of HSV-1 and HSV-2 as well as correlates and risk factors for prevalent and incident HSV-1 and HSV-2 mono- and co-infections; (2b) estimate HSV-1 and HSV-2 as risk factors for HIV acquisition, overall, and by race/ethnicity. (3) To determine prevalence and correlates of HSV/HPV co-infections and whether (a) HSV increases HPV risk, and (b) HPV infection or persistence increases HSV risk. An exploratory aim seeking to examine potential biological mechanisms linking HPV infection to HIV risk, will (1) compare local immunological response (measured via soluble cytokine levels) in the rectal microenvironment among those with and without HPV as a risk factor for HIV susceptibility. This study will provide much needed data on viral STIs in a racially/ethnically and socioeconomically diverse sample of YMSM as well as provide further insights on the potential for HPV, HSV-1, and HSV-2 to influence HIV transmission and acquisition risk.